a double-blind, randomized, dose response study of three doses of delavirdine mesylate (u-90152s) in combination with zidovudine (zdv) versus zdv alone in hiv-1 infected individuals with cd4 counts of 200-500mm3

Conditions: HIV Infections

Summary: part i: to evaluate the safety, tolerance, efficacy, and pharmacokinetics of three fixed doses of delavirdine mesylate (dlv) in combination with zidovudine (azt) versus azt alone in hiv-positive patients. part ii: to evaluate the safety, tolerance, efficacy, and pharmacokinetics of zdv plus 3tc with or without dlv versus zdv plus dlv in hiv-positive patients.

part i: patients are originally randomized to receive zdv plus dlv (dlv at 1 of 3 doses) or zdv plus placebo. as per amendment 3/7/96: part ii: patients are rerandomized from part i. arm i: zdv plus 3tc plus placebo. arm ii: zdv plus 3tc plus dlv. arm iii: zdv plus dlv (dlv at a higher dose than in the original protocol). arm iv: zdv plus dlv (no change from original; same treatment as arm iii). as per amendment 1/24/97: approximately 450 more patients will be enrolled in one of these 3 revised arms on part ii. half of these new patients will be anti-retroviral naive and half will be anti-retroviral experienced.

Eligibility criteria:
inclusion criteria patients must have: * hiv-1 seropositivity. * cd4 count 200-500 cells/mm3. * no active or acute (onset within the past month) opportunistic infections such as active cryptococcosis, pneumocystis carinii, herpes zoster, histoplasmosis, or cytomegalovirus (cmv). * consent of parent or guardian if less than 18 years of age. * understanding of potential risk to fetus related to study participation. * acceptable medical history, physical exam, ekg, and chest x-ray during screening. note: * patients with cutaneous kaposi's sarcoma requiring no systemic therapy are permitted. per amendment 3/7/96: * zdv therapy for 0-6 months prior to study entry. (part ii) prior medication: allowed: * prior azt (no more than 6 months total). exclusion criteria co-existing condition: patients with the following symptoms or conditions are excluded: * active tuberculosis that is sensitive to rifampin. * inability to swallow numerous tablets. * clinically significant active or acute medical problems, including progressive multifocal leukoencephalopathy, lymphoma, or malignancy requiring systemic therapy. * clinically significant hypersensitivity to piperazine-type drugs (e.g., antepar and stelazine). * grade 2 or worse baseline organ function. note: * hemophiliacs with grade 2 bilirubin, alkaline phosphatase, sgot, or sgpt will be considered if these values have been stable over the past year. note: * patients with suspected gilbert's syndrome will be considered if bilirubin is grade 2 or better. patients with the following prior conditions are excluded: * history of pancreatitis within the past 2 years. * history of clinically significant nervous system or muscle disease, seizure disorder, aids dementia, or psychiatric disorder that would preclude study compliance. * history of grade 2 or worse peripheral neuropathy. * intolerance to azt in previously treated patients. prior medication: excluded: * more than 6 months total of prior azt. * any prior ddc, d4t, 3tc, or ddi. * prior non-nucleoside reverse transcriptase inhibitors, including l-drugs, nevirapine, tibo, hept, delavirdine, atevirdine, and alpha-apa. * other investigational antiretroviral medications (including foscarnet) or immunomodulators (including all interferons) within 21 days prior to initial study drug dose. * prior prophylactic or therapeutic hiv-1 gp120 or 160 vaccines. * rifampin, rifabutin, astemizole, loratadine, or terfenadine within 21 days prior to initial study drug dose. * any unapproved investigational medication for any indication within 21 days prior to initial study drug dose. * any enzyme-inducing drugs known to affect cytochrome p450 3a, (e.g., ketoconazole, fluconazole, isoniazid, itraconazole, etc.) within 21 days prior to initial study drug dose. active substance abuse.

Keywords: drug therapy, combination acquired immunodeficiency syndrome aids-related complex antiviral agents zidovudine